Knowledge of rare genetic skeletal disorders has helped guide innovative treatment developments for osteoporosis, for example from our understanding of pycnodysostosis balicatib has emerged, as have anti-SOST antibodies from our experience of sclerosteosis and Van Buchems disease. Yet much high bone mass remains unexplained, better appreciation of which may translate into improved understanding of bone regulation and new therapeutic targets for future osteoporosis therapies.
This presentation will review disorders of osteoclast function known to cause osteopetrosis in adults, in addition to disorders of enhanced bone formation leading to increased bone mass, for example those caused by mutations affecting LRP5 and SOST, which up regulate wnt signalling. I will then describe the epidemiology of the high bone mass phenotype in the UK, which to date has not been explained by known mutations in LRP5 or SOST. I will also summarize some established diagnoses, aside from high bone mass, which can cause raised bone density on routine DXA scanning.
Finally, I will present details of the clinical features of unexplained high bone mass, which include increased skeletal and mandibular size and impaired buoyancy, suggestive of a mild skeletal dysplasia, although the underlying genetic basis remains to be determined. Interestingly, these high bone mass cases also have evidence of a metabolic phenotype as evidenced by an increase in fat mass, providing support for recent laboratory studies suggesting that important links exist between bone and fat metabolism.